Patch-based physiological sensor

ABSTRACT

The invention provides a body-worn patch sensor for simultaneously measuring a blood pressure (BP), pulse oximetry (SpO2), and other vital signs and hemodynamic parameters from a patient. The patch sensor features a sensing portion having a flexible housing that is worn entirely on the patient&#39;s chest and encloses a battery, wireless transmitter, and all the sensor&#39;s sensing and electronic components. It measures electrocardiogram (ECG), impedance plethysmogram (IPG), photoplethysmogram (PPG), and phonocardiogram (PCG) waveforms, and collectively processes these to determine the vital signs and hemodynamic parameters. The sensor that measures PPG waveforms also includes a heating element to increase perfusion of tissue on the chest.

BACKGROUND AND FIELD OF THE INVENTION 1. Field of the Invention

The invention relates to the use of systems that measure physiologicalparameters from patients located, e.g., in hospitals, clinics, and thehome.

2. General Background

There are a number of physiological parameters that can be assessed bymeasuring biometric signals from a patient. Some signals, such aselectrocardiogram (ECG), impedance plethysmogram (IPG),photoplethysmogram (PPG), and phonocardiogram (PCG) waveforms, aremeasured with sensors (e.g. electrodes, optics, microphones) thatconnect or attach directly to the patient's skin. Processing of thesewaveforms yields parameters such as heart rate (HR), heart ratevariability (HRV), respiration rate (RR), pulse oximetry (SpO2), bloodpressure (BP), stroke volume (SV), cardiac output (CO), and parametersrelated to thoracic impedance, e.g. thoracic fluid content (FLUIDS).Many physiological conditions can be identified from these parameterswhen they are obtained at a single point in time; others may requirecontinuous assessment over long or short periods of time to identifytrends in the parameters. In both cases, it is important to obtain theparameters consistently and with high repeatability and accuracy.

3. Known Devices and Relevant Physiology

Some devices that measure ECG waveforms are worn entirely on thepatient's body. These devices often feature simple, patch-type systemsthat include both analog and digital electronics connected directly tounderlying electrodes. Typically, these systems measure HR, HRV, RR,and, in some cases, posture, motion, and falls. Such devices aretypically prescribed for relatively short periods of time, e.g. for atime period ranging from a few days to several weeks. They are typicallywireless, and usually include technologies such as Bluetooth®transceivers to transmit information over a short range to a seconddevice, which typically includes a cellular radio to transmit theinformation to a web-based system.

Bioimpedance medical devices measure SV, CO, and FLUIDS by sensing andprocessing time-dependent ECG and IPG waveforms. Typically, thesedevices connect to patients through disposable electrodes adhered atvarious locations on a patient's body. Disposable electrodes thatmeasure ECG and IPG waveforms are typically worn on the patient's chestor legs and include: i) a conductive hydrogel that contacts the patient;ii) a Ag/AgCl-coated eyelet that contacts the hydrogel; iii) aconductive metal post that connects the eyelet to a lead wire or cableextending from the device; and iv) an adhesive backing that adheres theelectrode to the patient. Medical devices that measure BP, includingsystolic (SYS), diastolic (DIA), and mean (MAP) BP, typically usecuff-based techniques called oscillometry or auscultation, orpressure-sensitive catheters than are inserted in a patient's arterialsystem. Medical devices that measure SpO2 are typically optical sensorsthat clip onto a patient's finger or earlobes, or attach through anadhesive component to the patient's forehead.

SUMMARY OF THE INVENTION

In view of the foregoing, it would be beneficial to improve themonitoring of patients in hospitals, clinics, and the home with a patchsensor, like that described herein, that non-invasively measures vitalsigns such as HR, HRV, RR, SpO2, TEMP, and BP, along with complexhemodynamic parameters such as SV, CO, and FLUIDS. The patch sensoradheres to a patient's chest and continuously and non-invasivelymeasures the above-mentioned parameters without cuffs and wires. In thisway, it simplifies traditional protocols for taking such measurements,which typically involve multiple machines and can take several minutesto accomplish. The patch sensor wirelessly transmits information to anexternal gateway (e.g. tablet, smartphone, or non-mobile, plug-insystem) which can integrate with existing hospital infrastructure andnotification systems, such as a hospital electronic medical records(EMR) system. With such a system, caregivers can be alerted to changesin vital signs, and in response can quickly intervene to helpdeteriorating patients. The patch sensor can additionally monitorpatients from locations outside the hospital.

More particularly, the invention features a chest-worn patch sensor thatmeasures the following parameters from a patient: HR, PR, SpO2, RR, BP,TEMP, FLUIDS, SV, CO, and a set of parameters sensitive to bloodpressure and systemic vascular resistance called pulse arrival time(PAT) and vascular transit time (VTT).

The patch sensor also includes a motion-detecting accelerometer, fromwhich it can determine motion-related parameters such as posture, degreeof motion, activity level, respiratory-induced heaving of the chest, andfalls. Such parameters could determine, for example, a patient's postureor movement during a hospital stay. The patch sensor can operateadditional algorithms to process the motion-related parameters tomeasure vital signs and hemodynamic parameters when motion is minimizedand below a predetermined threshold, thereby reducing artifacts.Moreover, the patch sensor estimates motion-related parameters such asposture to improve the accuracy of calculations for vital signs andhemodynamic parameters.

Disposable electrodes on a bottom surface of the patch sensor secure itto the patient's body without requiring bothersome cables. Theelectrodes measure ECG and IPG waveforms. They easily connect (anddisconnect) to circuit boards contained within the sensor by means ofmagnets that are electrically connected to the circuit boards to providesignal-conducting electrical couplings. Prior to use, the electrodes aresimply held near the circuit boards, and magnetic attraction causes theelectrode patches to snap into proper position, thereby ensuring properpositioning of the electrodes on the patient's body.

Using light-emitting diodes (LEDs) operating in the red (e.g. 660 nm)and infrared (e.g. 900 nm) spectral regions, the patch sensor measuresSpO2 by pressing lightly against capillary beds in the patient's chest.A heating element on the bottom surface of the patch sensor contacts thepatient's chest and gently warms the underlying skin, thereby increasingperfusion of the tissue. Operating with reflection-mode optics, thepatch sensor measures PPG waveforms with both red and infraredwavelengths. SpO2 is processed from alternating and static components ofthese waveforms, as is described in more detail below.

The patch sensor measures all of the above-mentioned properties whilefeaturing a comfortable, easy-to-wear form factor. It is lightweight(about 20 grams) and powered with a rechargeable battery. During use, itrests on the patient's chest, where the disposable electrodes hold it inplace, as described in more detail below. The patient's chest is alocation that is unobtrusive, comfortable, removed from the hands, andable to hold the sensor without being noticeable to the patient. It isalso relatively free of motion compared to appendages such as the handsand fingers, and thus a sensor affixed to the chest region minimizesmotion-related artifacts. Such artifacts are compensated for, to somedegree, by the accelerometer within the sensor. And because the patchsensor is a small and therefore considerably less noticeable orobtrusive than various other physiological sensor devices, emotionaldiscomfort over wearing a medical device over an extended period of timeis reduced, thereby fostering long-term patient compliance for use ofthis device within a monitoring regimen.

Given the above, in one aspect, the invention provides a patch sensorfor simultaneously measuring BP and SpO2 from a patient. The patchsensor features a sensing portion having a flexible housing that is wornentirely on the patient's chest and encloses a battery, wirelesstransmitter, and all the sensor's sensing and electronic components. Thesensor measures ECG, IPG, PPG, and PCG waveforms, and collectivelyprocesses these determine BP and SpO2. The sensor that measures PPGwaveforms includes a heating element to increase perfusion of tissue onthe chest.

On its bottom surface, the flexible housing includes an analog opticalsystem, located proximal to one pair of the electrode contact points,that features a light source that generates radiation in both the redand infrared spectral ranges. This radiation separately irradiates aportion of the patient's chest disposed underneath the flexible housing.A photodetector detects the reflected radiation in the differentspectral ranges to generate analog red-PPG and infrared-PPG waveforms.

A digital processing system disposed within the flexible housingincludes a microprocessor and an analog-to-digital converter, and isconfigured to: 1) digitize the analog ECG waveform to generate a digitalECG waveform, 2) digitize the analog impedance waveform to generate adigital impedance waveform, 3) digitize the analog red-PPG waveform togenerate a digital red-PPG waveform, 4) digitize the analog infrared-PPGwaveform to generate a digital infrared-PPG waveform, and 5) digitizethe analog PCG waveform to generate a digital PCG waveform. Once thesewaveforms are digitized, numerical algorithms operating in embeddedcomputer code called ‘firmware’ process them to determine the parametersdescribed herein.

In another aspect, the invention provides a patch sensor for measuring aPPG waveform from a patient. The patch sensor includes a housing wornentirely on the patient's chest, and a heating element attached to thebottom surface of the housing so that, during use, it contacts and heatsan area of the patient's chest. An optical system is located on a bottomsurface of the housing and proximal to the heating element, and includesa light source that generates optical radiation that irradiates the areaof the patient's chest during a measurement. The sensor also features atemperature sensor in direct contact with the heating element, and aclosed-loop temperature controller within the housing and in electricalcontact with the heating element and the temperature sensor. During ameasurement, the closed-loop temperature controller receives a signalfrom the temperature sensor and, in response, controls an amount of heatgenerated by the heating element. A photodetector within the opticalsystem generates the PPG waveform by detecting radiation that reflectsoff the area of the patient's chest after it is heated by the heatingelement.

Heating tissue that yields the PPG waveform typically increases bloodflow (i.e. perfusion) to the tissue, thereby increasing the amplitudeand signal-to-noise ratio of the waveform. This is particularlyimportant for measurements made at the chest, where signals aretypically significantly weaker than those measured from moreconventional locations, such as the fingers, earlobes, and forehead.

In embodiments, the heating element features a resistive heater, such asa flexible film, metallic material, or polymeric material (e.g. Kapton®)that may include a set of embedded electrical traces that increase intemperature when electrical current passes through them. For example,the electrical traces may be disposed in a serpentine pattern tomaximize and evenly distribute the amount of heat generated during ameasurement. In other embodiments, the closed-loop temperaturecontroller includes an electrical circuit that applies an adjustablepotential difference to the resistive heater that is controlled by amicroprocessor. Preferably, the microcontroller adjusts the potentialdifference it applies to the resistive heater so that its temperature isbetween 40-45° C.

In embodiments, the flexible-film heating element features an openingthat transmits optical radiation generated by the light source so thatit irradiates an area of the patient's chest disposed underneath thehousing. In similar embodiments, the flexible film features a similaropening or set of openings that transmit optical radiation reflectedfrom the area of the patient's chest so that it is received by thephotodetector.

In still other embodiments, the housing further includes an ECG sensorthat features a set of electrode leads, each configured to receive anelectrode, that connect to the housing and electrically connect to theECG sensor. For example, in embodiments, a first electrode lead isconnected to one side of the housing, and a second electrode lead isconnected to an opposing side of the housing. During a measurement, theECG sensor receives ECG signals from both the first and secondelectrodes leads, and, in response, processes the ECG signals todetermine an ECG waveform.

In another aspect, the invention provides a sensor for measuring PPG andECG waveforms from a patient that is also worn entirely on the patient'schest. The sensor features an optical sensor, heating element, andtemperature sensor similar to that described above. The sensor alsoincludes a closed-loop temperature controller within the housing and inelectrical contact with the heating element, the temperature sensor, andthe processing system. The closed-loop temperature controller isconfigured to: 1) receive a first signal from the temperature sensor; 2)receive a second signal from the processing system corresponding to thesecond fiducial marker; 3) collectively process the first and secondsignals to generate a control parameter; and 4) control an amount ofheat generated by the heating element based on the control parameter.

In embodiments, a software system included in the processing systemdetermines a first fiducial marker within the ECG waveform that is oneof a QRS amplitude, a Q-point, a R-point, an S-point, and a T-wave.Similarly, the software system determines a second fiducial marker thatis one of an amplitude of a portion of the PPG waveform, a foot of aportion of the PPG waveform, and a maximum amplitude of a mathematicalderivative of the PPG waveform.

In embodiments, the closed-loop temperature controller features anadjustable voltage source, and is configured to control an amount ofheat generated by the heating element by adjusting the voltage source,e.g. the amplitude or frequency of a voltage generated by the voltagesource.

In another aspect, the invention provides a similar chest-worn sensorthat measures PPG waveforms from the patient, and from these SpO2values. The sensor features a similar heating element, temperature,closed-loop temperature controller, and optical system as describedabove. Here, the optical system generates optical radiation in both thered and infrared spectral regions. The sensor also includes an ECGsensor with at least two electrode leads and an ECG circuit thatgenerates an ECG waveform. During a measurement, a processing systemfeaturing a software system analyzes the ECG waveform to identify afirst fiducial marker, and based on the first fiducial marker,identifies a first set of fiducial markers within the red PPG waveform,and a second set of fiducial markers within the infrared PPG waveform.The processing system then collectively processes the first and secondset of fiducial markers to generate the SpO2 value.

In embodiments, for example, the first set of fiducials identified bythe software system features an amplitude of a baseline of the red PPGwaveform (RED(DC)) and an amplitude of a heartbeat-induced pulse withinthe red PPG waveform (RED(AC)), and the second set of fiducialsidentified by the software system features an amplitude of a baseline ofthe infrared PPG waveform (IR(DC)) and an amplitude of aheartbeat-induced pulse within the infrared PPG waveform (IR(AC)). Thesoftware system can be further configured to generate the SpO2 valuefrom a ratio of ratios (R) by analyzing the RED(DC), RED(AC), IR(DC),and IR(AC) using the following equations, or mathematical equivalentsthereof:

$R = \frac{{{RED}\left( {A\; C} \right)}/{{RED}\left( {D\; C} \right)}}{{{IR}\left( {A\; C} \right)}/{{IR}\left( {D\; C} \right)}}$${{Sp}\; O\; 2} = \frac{k_{1} - {k_{2} \times R}}{k_{3} - {k_{4} \times R}}$

where k₁, k₂, k₃, and k₄ are pre-determined constants. Typically, theseconstants are determined during a clinical study called a ‘breathe-downstudy’ using a group of patients. During the study, the concentration ofoxygen supplied to the patients is gradually lowered in sequential‘plateaus’ so that their SpO2 values changes from normal values (near98-100%) to hypoxic values (near 70%). As the concentration of oxygen islowered, reference SpO2 values are typically measured at each plateauwith a calibrated oximeter or a machine that measures oxygen contentfrom aspirated blood. These are the ‘true’ SpO2 values. R values arealso determined at each plateau from PPG waveforms measured by the patchsensor. The pre-determined constants k₁, k₂, k₃, and k₄ can then bedetermined by fitting these data using equations shown above.

In other aspects, the invention provides a chest-worn sensor similar tothat described above, that also includes an acoustic sensor formeasuring PCG waveforms. Here, the sensor is mated with a single-usecomponent that temporarily attaches to the sensor's housing and featuresa first electrode region positioned to connect to the first electrodecontact point, a second electrode region positioned to connect to thesecond electrode contact point, and an impedance-matching regionpositioned to attach to the acoustic sensor.

In embodiments, the impedance-matching region comprises a gel or plasticmaterial, and has an impedance at 100 kHz of about 220Ω. The acousticsensor can be a single microphone or a pair of microphones. Typically,the sensor includes an ECG sensor that yields a signal that is thenprocessed to determine a first fiducial point (e.g. a Q-point, R-point,S-point, or T-wave of a heartbeat-induced pulse in the ECG waveform). Aprocessing system within the sensor processes the PCG waveform todetermine the second fiducial point, which is either the S1 heart soundor S2 heart sound associated with a heartbeat-induced pulse in the PCGwaveform. The processing system then determines a time differenceseparating the first fiducial point and the second fiducial point, anduses this time difference to determine the patient's blood pressure.Typically a calibration measurement made by a cuff-based system is usedalong with the time difference to determine blood pressure.

In embodiments, the processor is further conjured to determine afrequency spectrum of the second fiducial point (using, e.g., a FourierTransform), and then uses this to determine the patient's bloodpressure.

In yet another aspect, the invention provides a chest-worn sensorsimilar to that described above. Here, the sensor features an opticalsystem, located on a bottom surface of the sensor's housing, thatincludes: 1) a light source that generates optical radiation thatirradiates an area of the patient's chest disposed underneath thehousing; and 2) a circular array of photodetectors that surround thelight source and detect optical radiation that reflects off the area ofthe patient's chest. As before, the area is heated with a heatingelement prior to a measurement.

Advantages of the invention should be apparent from the followingdetailed description, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing showing a patient wearing a patch sensoraccording to the invention;

FIG. 2A is a photograph back surface of the patch sensor shown in FIG.1;

FIG. 2B is a photograph of a front surface f the patch sensor shown inFIG. 1;

FIG. 3A is a photo back surface of the patch sensor shown in FIG. 1,with the optical sensor emphasized;

FIG. 3B is a schematic drawing of the optical sensor shown in FIG. 3A;

FIG. 4 is an exploded drawing of the optical sensor;

FIG. 5 is drawing of a patient lying in a hospital bed and wearing thepatch sensor according to the invention, with the patch sensortransmitting information through a gateway to a cloud-based system;

FIG. 6A is a time-dependent plot of an ECG waveform collected from apatient, along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6B is a time-dependent plot of a PCG waveform collectedsimultaneously and from the same patient as the ECG waveform shown inFIG. 6A, along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6C is a time-dependent plot of a PPG waveform collectedsimultaneously and from the same patient as the ECG waveform shown inFIG. 6A, along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6D is a time-dependent plot of a IPG waveform collectedsimultaneously and from the same patient as the ECG waveform shown inFIG. 6A, along with ‘x’ symbols marking fiducial points in the waveform;

FIG. 6E is a time-dependent plot of a mathematical derivative of the IPGwaveform shown in FIG. 6D, along with ‘x’ symbols marking fiducialpoints in the waveform;

7A is a time-dependent plot of ECG and PCG waveforms generated with thepatch sensor from a single heartbeat from a patient, along with circularsymbols marking fiducial points in these waveforms and indicating a timeinterval related to S2;

7B is a time-dependent plot of an ECG waveform and the mathematicalderivative of an IPG waveform generated with the patch sensor from asingle heartbeat from a patient, along with circular symbols markingfiducial points in these waveforms and indicating a time intervalrelated to B;

7C is a time-dependent plot of an ECG waveform and the mathematicalderivative of an IPG waveform generated with the patch sensor from asingle heartbeat from a patient, along with an arrow symbol marking aamplitude related to (dZ/dt)_(max);

FIG. 7D is a time-dependent plot of ECG and PPG waveforms generated withthe patch sensor from a single heartbeat from a patch patient, alongwith circular symbols marking fiducial points in these waveforms andindicating a time interval related to PAT;

FIG. 7E is a time-dependent plot of an ECG waveform and the mathematicalderivative of an IPG waveform generated with the patch sensor from asingle heartbeat from a patient, along with circular symbols markingfiducial points in these waveforms and indicating a time intervalrelated to C;

7F is a time-dependent plot of ECG and IPG waveforms generated with thepatch sensor from a single heartbeat from a patient, along with an arrowsymbol marking an amplitude related to Z₀;

FIG. 8A is a time-dependent plot of a PPG waveform measured with theoptical sensor of FIG. 3B before peat is applied to an underlyingsurface of a patient's skin;

FIG. 8B is a time-dependent plot of a PPG waveform measured with theoptical sensor of FIG. 3B after heat is applied to an underlying surfaceof a patient's skin;

FIG. 9 is a flow chart showing an algorithm used by the patch sensor tomeasure cuffless BP;

FIG. 10 is a table showing results from a clinical trial conducted on 21subjects that compared a cuffless BP measurement made by the patchsensor of FIG. 1 to a reference BP measurement performed usingauscultation; and

FIG. 11 is a schematic drawing showing a patient wearing an alternateembodiment of the patch sensor according to the invention.

DETAILED DESCRIPTION 1. Patch Sensor

As shown in FIGS. 1, 2A, and 2B, a patch sensor 10 according to theinvention measures ECG, PPG, PCG, and IPG waveforms from a patient 12,and from these calculates vital signs (HR, HRV, SpO2, RR, BP, TEMP) andhemodynamic parameters (FLUIDS, SV, and CO) as described in detailbelow. Once this information is determined, the patch sensor 10wirelessly transmits it to an external gateway, which then forwards itto a cloud-based system. In this way, a clinician can continuously andnon-invasively monitor the patient 12, who may be located in either thehospital or home.

The patch sensor 10 features two primary components: a centralsensing/electronics module 30 worn near the center of the patient'schest, and an optical sensor 36 worn near the patient's left shoulder. Aflexible, wire-containing cable 34 connects the centralsensing/electronics module 30 and the optical sensor 36. The opticalsensor 36 includes two electrode leads 47, 48 that connect to adhesiveelectrodes and help secure the patch sensor 10 (and particularly theoptical sensor 36) to the patient 12. The central sensing/electronicsmodule 30 features two ‘halves’ 39A, 39B, each housing sensing andelectronic components described in more detail below, that are separatedby a first flexible rubber gasket 38. A second flexible rubber gasket 51connects an acoustic module 32, which is positioned directly above thepatient's heart, to one of the halves 39B of the centralsensing/electronics module 30. Flexible circuits (not shown in thefigure) typically made of a Kapton® with embedded electrical tracesconnect fiberglass circuit boards (also not shown in the figure) withinthe acoustic module 32 and the two halves 39A, 39B of the centralsensing/electronics module 30.

Referring more specifically to FIG. 2A, the patch sensor 10 includes aback surface that, during use, contacts the patient's chest through aset of single-use, adhesive electrodes (not shown in the figure). Onehalf 39B of the central sensing/electronics module 30 includes twoelectrode leads 41, 42. These, coupled with the electrode leads 47, 48connected to the optical sensor 36, attach through a magnetic interfaceto the set of single-use electrodes. The electrode leads 41, 42, 47, 48form two ‘pairs’ of leads, wherein one of the leads 41, 47 in each pairinjects electrical current to measure IPG waveforms, and the other leads42, 48 in each pair sense bio-electrical signals that are then processedby electronics in the central sensing/electronics module 30 to determinethe ECG and IPG waveforms. The opposing half 39A of the centralsensing/electronics module 30 includes another electrode contact 43that, like electrode leads 41, 42, 47, 48, connects to a single-useelectrode (also not shown in the figure) to help secure the patch sensor10 to the patient 12.

The IPG measurement is made when the current-injecting electrodes 41, 47inject high-frequency (e.g. 100 kHz), low-amperage (e.g. 4 mA) currentinto the patient's chest. The electrodes 42, 48 sense a voltage thatindicates the impedance encountered by the injected current. The voltagepasses through a series of electrical circuits featuring analog filtersand differential amplifiers to, respectively, filter out and amplifysignal components related to the two different waveforms. One of thesignal components indicates the ECG waveform; another indicates the IPGwaveform. The IPG waveform has low-frequency (DC) and high-frequency(AC) components that are further filtered out and processed, asdescribed in more detail below, to determine different impedancewaveforms.

Use of a cable 34 to connect the central sensing/electronics module 30and the optical sensor 36 means the electrode leads (41, 42 in thecentral sensing/electronics module 30; 47, 48 in the optical sensor 36)can be separated by a relatively large distance when the patch sensor 10is attached to a patient's chest. For example, the optical sensor 36 canbe attached near the patient's left shoulder, as shown in FIG. 1. Suchseparation between the electrode leads 41, 42, 47, 48 typically improvesthe signal-to-noise ratios of the ECG and IPG waveforms measured by thepatch sensor 10, as these waveforms are determined from difference ofbio-electrical signals collected by the single-use electrodes, whichtypically increases with electrode separation. Ultimately this improvesthe accuracy of any physiological parameter detected from thesewaveforms, such as HR, HRV, RR, BP, SV, CO, and FLUIDS.

The acoustic module 32 includes a pair of solid-state acousticmicrophones 45, 46 that measure heart sounds from the patient 12. Theheart sounds are the ‘lub, dub’ sounds typically heard from the heartwith a stethoscope; they indicate when the underlying mitral andtricuspid (S1, or ‘lub’ sound) and aortic and pulmonary (S2, or ‘dub’sound) valves close (no detectable sounds are generated when the valvesopen). With signal processing, the heart sounds yield a PCG waveformthat is used along with other signals to determine BP, as is describedin more detail below. Two solid-state acoustic microphones 45, 46 areused to provide redundancy and better detect the sounds. The acousticmodule 32, like the half 39A of the central sensing/electronics module30, includes an electrical contact 43 that connects to a single-useelectrode (also not shown in the figure) to help secure the patch sensor10 to the patient 12.

The optical sensor 36 attaches to the central sensing/electronics module30 through the flexible cable 34, and features an optical system 60 thatincludes an array of photodetectors 62, arranged in a circular pattern,that surround a LED 61 that emits radiation in the red and infraredspectral regions. During a measurement, sequentially emitted red andinfrared radiation from the LED 61 irradiates and reflects offunderlying tissue in the patient's chest, and is detected by the arrayof photodetectors 62. The detected radiation is modulated by bloodflowing through capillary beds in the underlying tissue. Processing thereflected radiation with electronics in the central sensing/electronicsmodule 30 results in PPG waveforms corresponding to the red and infraredradiation, which as described below are used to determine BP and SpO2.

The patch sensor 10 also typically includes a three-axis digitalaccelerometer and a temperature sensor (not specifically identified inthe figure) to measure, respectively, three time-dependent motionwaveforms (along x, y, and z-axes) and TEMP values.

Referring more specifically to FIG. 2B, the top side of the centralsensing/electronics module 30 includes a magnetic post 55 that connectsto an oppositely polarized magnet (not shown in the figure) that liesunderneath a circular boss 56 located on top of the optical sensor 36.The magnetic post 55 connects to the circular boss 56 when the patchsensor 10 is stored and not in use.

FIGS. 3A, 3B, and 4 show the optical sensor 36 in more detail. Asdescribed above, the sensor 36 features an optical system 60 with acircular array of photodetectors 62 (six unique detectors are shown inthe figure, although this number can be between three and ninephotodetectors) that surround a dual-wavelength LED 61 that emits redand infrared radiation. A heating element featuring a thin Kapton® film65 with embedded electrical conductors arranged in a serpentine patternis adhered to the bottom surface of the optical sensor 36. Otherpatterns of electrical conductors can also be used. The Kapton® film 65features cut-out portions that pass radiation emitted by the LED 61 anddetected by the photodetectors 62 after it reflects off the patient'sskin. A tab portion 67 on the thin Kapton® film 65 folds over so it canplug into a connector 74 on a fiberglass circuit board 80. Thefiberglass circuit board 80 supports and provides electrical connectionsto the array of photodetectors 62 and the LED 61. During use, softwareoperating on the patch sensor 10 controls power-management circuitry onthe fiberglass circuit board 80 to apply a voltage to the embeddedconductors within the thin Kapton® film 65, thereby passing electricalcurrent through them. Resistance of the embedded conductors causes thefilm 65 to gradually heat up and warm the underlying tissue. The appliedheat increases perfusion (i.e. blood flow) to the tissue, which in turnimproves the signal-to-noise ratio of the PPG waveform. This is shown inFIG. 8A, which shows a PPG waveform measured before heat is applied, andFIG. 8B, which shows a PPG waveform measured after heat is applied withthe Kapton® film 65. As is clear from the figures, heat increases theperfusion underneath the optical sensor 36. This, in turn, dramaticallyimproves the signal-to-noise ratio of heartbeat-induced pulses in thePPG waveform. This is important for the patch sensor's opticalmeasurements, as PPG waveforms measured from the chest typically have asignal-to-noise ratio that is 10-100× weaker than similar waveformsmeasured from typical locations used by pulse oximeters, e.g. thefingers, earlobes, and forehead. PPG waveforms with improvedsignal-to-noise ratios typically improve the accuracy of BP and SpO2measurements made by the patch sensor 10. The fiberglass circuit board80 also includes a temperature sensor 76 that integrates with thepower-management circuitry, allowing the software to operate in aclosed-loop manner to carefully control and adjust the appliedtemperature. Here, ‘closed-loop manner’ means that the software analyzesamplitudes of heartbeat-induced pulses the PPG waveforms, and, ifnecessary, increases the voltage applied to the Kapton® film 65 toincrease its temperature and maximize the heartbeat-induced pulses inthe PPG waveforms. Typically, the temperature is regulated at a level ofbetween 41° C. and 42° C., which has been shown to not damage theunderlying tissue, and is also considered safe by the U.S. Food and DrugAdministration (FDA).

A plastic housing 44 featuring a top portion 53 and a bottom portion 70enclose the fiberglass circuit board 80. The bottom portion 70 alsosupports the Kapton® film 65, has cut-out portions 86 that passesoptical radiation, and includes a pair of snaps 84, 85 that connect tomated components on the top portion 53. The top portion also includes apair of ‘wings’ that enclose the electrode leads 47, 48 which, duringuse, connect to the single-use, adhesive electrodes (not shown in thefigure) that secure the optical sensor 36 to the patient. Theseelectrode leads 47, 48 also measure electrical signals that are used forthe ECG and IPG measurements. The top portion 53 also includes amechanical strain relief 68 that supports the cable 34 connecting theoptical sensor 36 to the central sensing/electronics module 30.

The patch sensor 10 typically measures waveforms at relatively highfrequencies (e.g. 250 Hz). An internal microprocessor running firmwareprocesses the waveforms with computational algorithms to generate vitalsigns and hemodynamic parameters with a frequency of about once everyminute. Examples of algorithms are described in the following co-pendingand issued patents, the contents of which are incorporated herein byreference: “NECK-WORN PHYSIOLOGICAL MONITOR,” U.S. Ser. No. 14/975,646,filed Dec. 18, 2015; “NECKLACE-SHAPED PHYSIOLOGICAL MONITOR,” U.S. Ser.No. 14/184,616, filed Aug. 21, 2014; and “BODY-WORN SENSOR FORCHARACTERIZING PATIENTS WITH HEART FAILURE,” U.S. Ser. No. 14/145,253,filed Jul. 3, 2014.

The patch sensor 10 shown in FIGS. 1, 2A, 2B, 3A, 3B, and 4 is designedto maximize comfort and reduce ‘cable clutter’ when deployed on apatient, while at the same time optimizing the ECG, IPG, PPG, and PCGwaveforms it measures to determine physiological parameters such as HR,HRV, BP, SpO2, RR, TEMP, FLUIDS, SV, and CO. The first 38 and second 51flexible rubber gaskets allow the sensor 10 to flex on a patient'schest, thereby improving comfort. The central sensing/electronics module30 positions the first pair of electrode leads 41, 42 above the heart,where bio-electrical signals are typically strong, while thecable-connected optical sensor 36 positions the second pair of electrodeleads 47, 48 near the shoulder, where they have large separation fromthe first pair. As described above, this configuration results in idealECG and IPG waveforms. The acoustic module 32 is positioned directlyabove the patient's heart, and includes multiple acoustic sensors 45, 46to optimize PCG waveforms and the heart sounds indicated therein. Andthe optical sensor is positioned near the shoulder, wherein underlyingcapillary beds typically result in PPG waveforms having goodsignal-to-noise ratios, especially when perfusion is increased by thesensor's heating element.

This patch sensor's design also allows it to comfortably fit both maleand female patients. An additional benefit of its chest-wornconfiguration is reduction of motion artifacts, which can distortwaveforms and cause erroneous values of vital signs and hemodynamicparameters to be reported. This is due, in part, to the fact that duringeveryday activities, the chest typically moves less than the hands andfingers, and subsequent artifact reduction ultimately improves theaccuracy of parameters measured from the patient.

2. Use Cases

As shown in FIG. 5, in a preferred embodiment, a patch sensor 10according to the invention is designed to monitor a patient 12 during ahospital stay. Typically, the patient 12 is situated in a hospital bed11. As indicated above, in a typical use case, the patch sensor 10continuously measures numerical and waveform data, and then sends thisinformation wirelessly (as indicated by arrow 77) to a gateway 22, whichcan be a number of different devices. For example, the gateway 22 can beany device operating a short-range wireless (e.g. Bluetooth®) wirelesstransmitter, e.g. a mobile telephone, tablet computer, vital signmonitor, central station (e.g. nursing station in a hospital), hospitalbed, ‘smart’ television set, single-board computer, or a simple plug-inunit. The gateway 22 wirelessly forwards information (as indicated byarrow 87) from the patch sensor 10 to a cloud-based software system 200.Typically, this is done with a wireless cellular radio, or one based onan 802.11a-g protocol. There, it can be consumed and processed by avariety of different software systems, such as an EMR, a third-partysoftware system, or a data-analytics engine.

In another embodiment, the sensor collects data and then stores it ininternal memory. The data can then be sent wirelessly (e.g. to thecloud-based system, EMR, or central station) at a later time. Forexample, in this case, the gateway 22 can include an internal Bluetooth®transceiver that sequentially and automatically pairs with each sensorattached to a charging station. Once all the data collected during useare uploaded, the gateway then pairs with another sensor attached to thecharging station and repeats the process. This continues until data fromeach sensor is downloaded.

In other embodiments, the patch sensor can be used to measure ambulatorypatients, patients undergoing dialysis in either the hospital, clinic,or at home, or patients waiting to see a doctor in a medical clinic.Here, the patch sensor can transmit information in real time, or storeit in memory for transmission at a later time.

3. Determining Cuffless Blood Pressure

The patch sensor determines BP by collectively processing time-dependentECG, IPG, PPG, and PCG waveforms, as shown in FIGS. 6A-E. Each waveformis typically characterized by a heartbeat-induced ‘pulse’ that isaffected in some way by BP. More specifically, embedded firmwareoperating on the patch sensor processes pulses in these waveforms with‘beatpicking’ algorithms to determine fiducial makers corresponding tofeatures of each pulse; these markers are then processed withalgorithms, described below, to determine BP. In FIGS. 6A-E, thefiducial makers for pulses within the ECG, IPG, PPG, and PCG waveformsare indicated with ‘x’ symbols.

An ECG waveform measured by the patch sensor is shown in FIG. 6A. Itincludes a heartbeat-induced QRS complex that informally marks thebeginning of each cardiac cycle. FIG. 6B shows a PCG waveform, which ismeasured with the acoustic module and features the S1 and S2 heartsounds. FIG. 6C shows a PPG waveform, which is measured by the opticalsensor, and indicates volumetric changes in underlying capillariescaused by heartbeat-induced blood flow. The IPG waveform includes bothDC (Z₀) and AC (dZ(t)) components: Z₀ indicates the amount of fluid inthe chest by measuring underlying electrical impedance, and representsthe baseline of the IPG waveform; dZ(t), which is shown in FIG. 6D,tracks blood flow in the thoracic vasculature and represents thepulsatile components of the IPG waveform. The time-dependent derivativeof dZ(t)—dZ(t)/dt—includes a well-defined peak that indicates themaximum rate of blood flow in the thoracic vasculature, and is shown inFIG. 6E.

Each pulse in the ECG waveform (FIG. 6A) features a QRS complex thatdelineates a single heartbeat. Feature-detection algorithms operating infirmware on the patch sensor calculate time intervals between the QRScomplex and fiducial markers on each of the other waveforms. Forexample, the time separating a ‘foot’ of a pulse in the PPG waveform(FIG. 6C) and the QRS complex is referred to as PAT. PAT relates to BPand systemic vascular resistance. During a measurement, the patch sensorcalculates PAT and VTT which is a time difference between fiducialmarkers in waveforms other than ECG, e.g. the S1 or S2 points in a pulsein the PCG waveform (FIG. 6B) and the foot of the PPG waveform (FIG.6C). Or the peak of a pulse in the dZ(t)/dt waveform (FIG. 6E) and thefoot of the PPG waveform (FIG. 6C). In general, any set oftime-dependent fiducials determined from waveforms other than ECG can beused to determine VTT. Collectively, PAT, VTT, and other time-dependentparameters extracted from pulses in the four physiologic waveforms arereferred to herein as ‘INT’ values. Additionally, firmware in the patchsensor calculates information about the amplitudes of heartbeat-inducedpulses in some of the waveforms; these are referred to herein as ‘AMP’values. For example, the amplitude of the pulse in the derivative of theAC component of the IPG waveform ((dZ(t)/dt)max as shown in FIG. 6E)indicates the volumetric expansion and forward blood flow of thethoracic arteries, and is related to SYS and the contractility of theheart.

The general model for calculating SYS and DIA involves extracting acollection of INT and AMP values from the four physiologic waveformsmeasured by the patch sensor. FIGS. 7A-F, for example, show differentINT and AMP values that may correlate to BP. INT values include the timeseparating R and S2 from a pulse in the PCG waveform (RS2, shown in FIG.7A); the time separating R and the base of a derivative of a pulse fromthe AC component of the IPG waveform (RB, FIG. 7B); the time separatingR and the foot of a pulse in the PPG waveform (PAT, FIG. 7D); and thetime separating R and the maximum of a derivative of a pulse from the ACcomponent of the IPG waveform (RC, FIG. 7E). AMP values include themaximum value of a derivative of a pulse from the AC component of theIPG waveform ((dZ(t)/dt)max, FIG. 7C); and the maximum value of the DCcomponent of the IPG waveform (Z₀, FIG. 7F). Any of these parameters maybe used, in combination with a calibration defined below, to determineblood pressure.

The method for determining BP according to the invention involves firstcalibrating the BP measurement during a short initial period, and thenusing the resulting calibration for subsequent measurements. Thecalibration process typically lasts for about 5 days. It involvesmeasuring the patient multiple (e.g. 2-4) times with a cuff-based BPmonitor employing oscillometry, while simultaneously collecting the INTand AMP values like those shown in FIGS. 7A-F. Each cuff-basedmeasurement results in separate values of SYS, DIA, and MAP. Inembodiments, one of the cuff-based BP measurements is coincident with a‘challenge event’ that alters the patient's BP, e.g. squeezing ahandgrip, changing posture, or raising their legs. The challenge eventstypically impart variation in the calibration measurements; this canhelp improve the ability of the calibration to track BP swings.Typically, the patch sensor and cuff-based BP monitor are in wirelesscommunication with each other; this allows the calibration process to befully automated, e.g. information between the two systems can beautomatically shared without any user input. Processing the INT and AMPvalues, e.g. using the method shown in FIG. 9 and described in moredetail below, results in a ‘BP calibration’. This includes initialvalues of SYS and DIA, which are typically averaged from the multiplemeasurements made with the cuff-based BP monitor, along with apatient-specific model that is used in combination with selected INT andAMP values to cufflessly determine the patient's blood pressure. Thecalibration period (about 5 days), is consistent with a conventionalhospital stay; after this, the patch sensor typically requires a newcalibration to ensure accurate BP measurements.

FIG. 9 is a flowchart that indicates how the BP calibration isdetermined, and how cuffless BP values are then calculated using the BPcalibration. The process starts by collecting calibration data (step150) that includes values of SYS and DIA. These data are collected alongwith INT and AMP values for each measurement. Typically, this process isrepeated four times, with one instance coinciding with a challengeevent, as described above. Using embedded firmware operating on thepatch sensor, the calibration data is then ‘fit’ with multiple linearmodels (step 151) to determine which individual INT and AMP values bestpredict the patient's SYS and DIA values, as measured with thecuff-based BP monitor. Here, the term ‘fit’ means using an iterativealgorithm, such as a Levenberg-Marquardt (LM) fitting algorithm, toprocess the INT/AMP values to estimate the calibration data. The LMalgorithm is also known as the damped least-squares (DLS) method, and isused to solve non-linear least squares problems. These minimizationproblems arise especially in least squares curve fitting. The INT andAMP values selected using the LM algorithm are those that yield theminimum error between the fits and calibration data (step 152); here,the error can be the ‘residual’ of the fit, or alternatively a root-meansquared error (RMSE) between the fit and the calculated data. Typically,two ideal INT/AMP values are selected with this process. Once selected,the two ideal INT/AMP values are then combined into a single,two-parameter linear model, which is then used to fit calibration dataonce again (step 153). The fitting coefficients that are determined fromthis fitting process, along with the average, initial values of SYS andDIA determined from the calibration data, represent the BP calibration(step 154). This process is done independently for SYS and DIA, meaningthat one set of INT/AMP values may be used for the BP calibration forSYS, and another set used for the BP calibration for DIA.

Once determined, the BP calibration is then used to calculate cufflessBP values going forward. Specifically, for a post-calibration cufflessmeasurement, the selected INT/AMP values (2 total) are measured from thetime-dependent ECG, IPG, PPG, and PCG waveforms. These values are thencombined in a linear model with the BP calibration (fitting coefficientsand average, initial values of SYS and DIA), which is then used tocalculate BP (step 155).

4. Clinical Results

The table 170 shown in FIG. 10 indicates the efficacy of this approachfor both SYS and DIA. Data in the table were collected using a clinicalstudy performed over a 3-day period with 21 subjects. In total, theclinical study was conducted over a 2-week period, starting in December2017 at a single study site in the greater San Diego area. Allmeasurements were made while the subjects rested in a supine position ina hospital bed. A BP calibration was determined on the first day of thestudy (Day 1) for each subject using the approach described above andshown in FIG. 9. Once the BP calibration was determined, the subject wasdismissed, and then returned 2 days later (Day 3) for a cuffless BPmeasurement. The BP calibration on Day 1 was used along with theselected INT/AMP values to determine cuffless BP values on Day 3, where10 measurements were made periodically over a period of about 2 hours,all while the subject was resting in a supine position. For mostsubjects, at least one of the 10 measurements featured a challengeevent, as described above, which typically elevated the subject's BP.And for each of the 10 measurements, cuffless BP values were compared toreference BP values measured with a ‘gold-standard technique’, which inthis case was a clinician measuring blood pressure using a techniquecalled auscultation, which is performed using a cuff-basedsphygmomanometer.

The table 170 includes the following columns:

Column 1—subject number

Column 2—maximum reference value of SYS (units mmHg)

Column 3—range in reference values of SYS (units mmHg)

Column 4—standard deviation calculated from the difference between thereference and cuffless values of SYS measured on Day 3 (10 measurementstotal, units mmHg)

Column 5—bias calculated from the difference between the reference andcuffless values of SYS measured on Day 3 (10 measurements total, unitsmmHg)

Column 6—selected INT/AMP values used in the cuffless measurement of SYS

Column 7—maximum reference value of DIA (units mmHg)

Column 8—range in reference values of DIA (units mmHg)

Column 9—standard deviation calculated from the difference between thereference and cuffless values of DIA measured on Day 3 (10 measurementstotal, units mmHg)

Column 10—bias calculated from the difference between the reference andcuffless values of DIA measured on Day 3 (10 measurements total, unitsmmHg)

Column 11—selected INT/AMP values used in the cuffless measurement ofDIA

As shown in the table 170, the average standard deviation and biascalculated from the difference between the reference and cuffless valuesof SYS measured on Day 3 were 7.0 and 0.6 mmHg, respectively. Thecorresponding values for DIA were 6.2 and −0.4 mmHg, respectively. Thesevalues are within those recommended by the U.S. FDA (standard deviationless than 8 mmHg, bias less than ±5 mmHg), and thus indicate that thecuffless BP measurement of the invention has suitable accuracy.

5. Alternate Embodiments

The patch sensor described herein can have a form factor that differsfrom that shown in FIG. 1. FIG. 11, for example, shows such an alternateembodiment Like the preferred embodiment described above, the patchsensor 210 in FIG. 11 features two primary components: a centralsensing/electronics module 230 worn near the center of the patient'schest, and an optical sensor 236 worn near the patient's left shoulder.Electrode leads 241, 242 measure bio-electrical signals for the ECG andIPG waveforms and secure the central sensing/electronics module 230 tothe patient 12, similar to the manner as described above. A flexible,wire-containing cable 234 connects the central sensing/electronicsmodule 230 and the optical sensor 236. In this case, the centralsensing/electronics module 230 features a substantially rectangularshape, as opposed to a substantially circular shape shown in FIG. 1. Theoptical sensor 236 includes two electrode leads 247, 248 that connect toadhesive electrodes and help secure the patch sensor 210 (andparticularly the optical sensor 236) to the patient 12. The distalelectrode lead 248 connects to the optical sensor through anarticulating arm 245 that allows it to extend further out near thepatient's shoulder, thereby increasing its separation from the centralsensing/electronics module 230.

The central sensing/electronics module 230 features two ‘halves’ 239A,239B, each housing sensing and electronic components that are separatedby a flexible rubber gasket 238. The central sensing/electronics module230 connects an acoustic module 232, which is positioned directly abovethe patient's heart. Flexible circuits (not shown in the figure)typically made of a Kapton® with embedded electrical traces) connectfiberglass circuit boards (also not shown in the figure) within the twohalves 239A, 239B of the central sensing/electronics module 230.

The electrode leads 241, 242, 247, 248 form two ‘pairs’ of leads,wherein one of the leads 241, 247 injects electrical current to measureIPG waveforms, and the other leads 242, 248 sense bio-electrical signalsthat are then processed by electronics in the centralsensing/electronics module 230 to determine the ECG and IPG waveforms.

The acoustic module 232 includes one or more solid-state acousticmicrophones (not shown in the figure, but similar to that shown inFIG. 1) that measure heart sounds from the patient 12. The opticalsensor 236 attaches to the central sensing/electronics module 30 throughthe flexible cable 234, and features an optical system (also not shownin the figure, but similar to that shown in FIG. 1) that includes anarray of photodetectors, arranged in a circular pattern, that surround aLED that emits radiation in the red and infrared spectral regions.During a measurement, sequentially emitted red and infrared radiationemitted from the LED irradiates and reflects off underlying tissue inthe patient's chest, and is detected by the array of photodetectors.

In other embodiments, an amplitude of either the first or second (orboth) heart sound is used to predict blood pressure. Blood pressuretypically increases in a linear manner with the amplitude of the heartsound. In embodiments, a universal calibration describing this linearrelationship may be used to convert the heart sound amplitude into avalue of blood pressure. Such a calibration, for example, may bedetermined from data collected in a clinical trial conducted with alarge number of subjects. Here, numerical coefficients describing therelationship between blood pressure and heart sound amplitude aredetermined by fitting data determined during the trial. Thesecoefficients and a linear algorithm are coded into the sensor for useduring an actual measurement. Alternatively, a patient-specificcalibration can be determined by measuring reference blood pressurevalues and corresponding heart sound amplitudes during a calibrationmeasurement, which proceeds an actual measurement. Data from thecalibration measurement can then be fit as described above to determinethe patient-specific calibration, which is then used going forward toconvert heart sounds into blood pressure values.

Both the first and second heart sounds are typically composed of acollection, or ‘packet’ of acoustic frequencies. Thus, when measured inthe time domain, the heart sounds typically feature a number of closelypacked oscillations within to the packet. This can make it complicatedto measure the amplitude of the heart sound, as no well-defined peak ispresent. To better characterize the amplitude, a signal-processingtechnique can be used to draw an envelope around the heart sound, andthen measure the amplitude of the envelope. One well-known technique fordoing this involves using a Shannon Energy Envelogram (E(t)), where eachdata point within E(t) is calculated as shown below:

$E_{average} = {{- \frac{1}{N}}{\sum\limits_{t = 1}^{N}\left\lbrack {{{PCG}^{2}(t)} \times {\log \left( {{PCG}^{2}(t)} \right)}} \right\rbrack}}$

where N is the window size of E(t). In embodiments, other techniques fordetermining the envelope of the heart sound can also be used.

Once the envelope is calculated, its amplitude can be determined usingstandard techniques, such as taking a time-dependent derivative andevaluating a zero-point crossing. Typically, before using it tocalculate blood pressure, the amplitude is converted into a normalizedamplitude by dividing it by an initial amplitude value measured from anearlier heart sound (e.g., one measured during calibration). Anormalized amplitude means the relative changes in amplitude are used tocalculate blood pressure; this typically leads to a more accuratemeasurement.

In other embodiments, an external device may be used to determine howwell the acoustic sensor is coupled to the patient. Such an externaldevice, for example, may be a piezoelectric ‘buzzer’, or somethingsimilar, that generates an acoustic sound and is incorporated into thepatch-based sensor, proximal to the acoustic sensor. Before ameasurement, the buzzer generates an acoustic sound at a known amplitudeand frequency. The acoustic sensor measures the sound, and then comparesits amplitude (or frequency) to other historical measurements todetermine how well the acoustic sensor is coupled to the patient. Anamplitude that is relatively low, for example, indicates that the sensoris poorly coupled. This scenario may result in an alarm alerting theuser that the sensor should be reapplied.

In other alternative embodiments, the invention may use variation ofalgorithms for finding INT and AMP values, and then processing these todetermine BP and other physiological parameters. For example, to improvethe signal-to-noise ratio of pulses within the IPG, PCG, and PPGwaveforms, embedded firmware operating on the patch sensor can operate asignal-processing technique called ‘beatstacking’. With beatstacking,for example, an average pulse (e.g. Z(t)) is calculated from multiple(e.g. seven) consecutive pulses from the IPG waveform, which aredelineated by an analysis of the corresponding QRS complexes in the ECGwaveform, and then averaged together. The derivative of Z(t)—dZ(t)/dt—isthen calculated over an 7-sample window. The maximum value of Z(t) iscalculated, and used as a boundary point for the location of[dZ(t)/dt]_(max). This parameter is used as described above. In general,beatstacking can be used to determine the signal-to-noise ratio of anyof the INT/AMP values described above.

In other embodiments, the BP calibration process indicated by the flowchart shown in FIG. 9 can be modified. For example, it may select morethan two INT/AMP values to use for the multi-parameter linear fittingprocess. And the BP calibration data may be calculated with less than ormore than four cuff-based BP measurements. In still other embodiments, anon-linear model (e.g. one using a polynomial or exponential function)may be used to fit the calibration data.

In still other embodiments, a sensitive accelerometer can be used inplace of the acoustic sensor to measure small-scale, seismic motions ofthe chest driven by the patient's underlying beating heart. Suchwaveforms are referred to as seismocardiogram (SCG) and can be used inplace of (or in concert with) PCG waveforms.

These and other embodiments of the invention are deemed to be within thescope of the following claims.

What is claimed is:
 1. A sensor for measuring electrocardiogram (ECG)and phonocardiogram (PCG) waveforms from a patient, the sensorcomprising: a housing and worn entirely on the patient's chest andenclosing the sensor's electronic and computational components,including: a pair of electrode contact points disposed on a bottomsurface of the housing and comprising a first electrode contact pointand a second electrode contact point, with each electrode contact pointconfigured to sense a bio-electric signal from the patient; an ECGsystem in electrical contact with the pair of electrode contact points,the ECG system configured to receive the bio-electric signals from theelectrode contact points and, after processing them, generate an ECGwaveform; a PCG system comprising an acoustic sensor configured todetect acoustic sounds from the patient's heart and process them togenerate a PCG waveform; and a processing system comprising amicroprocessor configured to process the ECG waveform to determine afirst fiducial point, and further configured to process the firstfiducial point and the PCG waveform to determine a second fiducial pointfrom the PCG waveform; and a single-use component that temporarilyattaches to the housing and comprises a first electrode regionpositioned to connect to the first electrode contact point, a secondelectrode region positioned to connect to the second electrode contactpoint, and an impedance-matching region positioned to attach to theacoustic sensor.
 2. The sensor of claim 1, wherein theimpedance-matching region comprises a gel material.
 3. The sensor ofclaim 1, wherein the impedance-matching region comprises a plasticmaterial.
 4. The sensor of claim 1, wherein the impedance-matchingregion has an impedance at 100 kHz of about 220Ω.
 5. The sensor of claim1, wherein the housing comprises a flexible hinge separating a leftportion worn on a left-hand side of the patient's chest, and a rightportion worn on a right-hand side of the patient's chest, with theflexible hinge configured to be worn proximal to the center of thepatient's chest when the housing is worn by the patient.
 6. The sensorof claim 5, wherein PCG system connects to the left portion of thehousing.
 7. The sensor of claim 6, wherein the PCG system attaches tothe patient's chest over a region proximal to their third intercostalspace when the housing is worn by the patient.
 8. The sensor of claim 1,wherein the acoustic sensor is a single microphone.
 9. The sensor ofclaim 8, wherein the acoustic sensor is a pair of microphones.
 10. Thesensor of claim 1, wherein the microprocessor is configured to processthe ECG waveform to determine the first fiducial point, which is eitherthe Q-point, R-point, S-point, or T-wave of a heartbeat-induced pulse inthe ECG waveform.
 11. The sensor of claim 10, wherein the microprocessoris configured to process the PCG waveform to determine the secondfiducial point, which is either the S1 heart sound or S2 heart sound ofa heartbeat-induced pulse in the PCG waveform.
 12. The sensor of claim11, wherein the microprocessor is further configured to determine a timedifference separating the first fiducial point and the second fiducialpoint.
 13. The sensor of claim 13, wherein the microprocessor is furtherconfigured to determine a blood pressure value from the time difference.14. The sensor of claim 11, wherein the microprocessor is furtherconjured to determine a frequency spectrum of the second fiducial point.15. The sensor of claim 14, wherein the microprocessor is furtherconfigured to determine a blood pressure value from the frequencyspectrum.
 16. A sensor for measuring a blood pressure value from apatient by processing electrocardiogram (ECG) and phonocardiogram (PCG)waveforms, the sensor comprising: a housing and worn entirely on thepatient's chest and enclosing the sensor's electronic and computationalcomponents, including: a pair of electrode contact points disposed on abottom surface of the housing and comprising a first electrode contactpoint and a second electrode contact point, with each electrode contactpoint configured to sense a bio-electric signal from the patient; an ECGsystem in electrical contact with the pair of electrode contact points,the ECG system configured to receive the bio-electric signals from theelectrode contact points and, after processing them, generate an ECGwaveform; a PCG system comprising an acoustic sensor configured todetect acoustic sounds from the patient's heart and process them togenerate a PCG waveform; and a processing system comprising amicroprocessor configured to process: 1) the ECG waveform to determine afirst fiducial point; 2) the first fiducial point and the PCG waveformto determine a second fiducial point; 3) the first and second fiducialpoint to determine a time difference; and 4) the time difference todetermine the blood pressure value; and a single-use component thattemporarily attaches to the housing and comprises a first electroderegion positioned to connect to the first electrode contact point, asecond electrode region positioned to connect to the second electrodecontact point, and an impedance-matching region positioned to attach tothe acoustic sensor.
 17. The sensor of claim 16, wherein theimpedance-matching region comprises a gel material.
 18. The sensor ofclaim 16, wherein the impedance-matching region comprises a plasticmaterial.
 19. The sensor of claim 16, wherein the impedance-matchingregion has an impedance at 100 kHz of about 220Ω.
 20. The sensor ofclaim 1, wherein the housing comprises a flexible hinge separating aleft portion worn on a left-hand side of the patient's chest, and aright portion worn on a right-hand side of the patient's chest, with theflexible hinge configured to be worn proximal to the center of thepatient's chest when the housing is worn by the patient.
 21. The sensorof claim 20, wherein PCG system connects to the left portion of thehousing.
 22. The sensor of claim 21, wherein the PCG system attaches tothe patient's chest over a region proximal to their third intercostalspace when the housing is worn by the patient.
 23. The sensor of claim16, wherein the acoustic sensor is a single microphone.
 24. The sensorof claim 23, wherein the acoustic sensor is a pair of microphones. 25.The sensor of claim 16, wherein the microprocessor is configured toprocess the ECG waveform to determine the first fiducial point, which iseither the Q-point, R-point, S-point, or T-wave of a heartbeat-inducedpulse in the ECG waveform.
 26. The sensor of claim 25, wherein themicroprocessor is configured to process the PCG waveform to determinethe second fiducial point, which is either the S1 heart sound or S2heart sound of a heartbeat-induced pulse in the PCG waveform.